Reconstruction of shear wave speed in tissue-mimicking phantoms from aliased pulse-echo imaging of high-frequency wavefields.

Quantitative elasticity estimation in medical and industrial applications may benefit from advancements in reconstruction of shear wave speed with enhanced resolution. Here, shear wave speed is reconstructed from pulse-echo ultrasound imaging of elastic waves induced by high-frequency (>400 Hz), time-harmonic mechanical excitation. Particle displacement in shear wavefields is mapped from measured interframe phase differences with compensation for timing of multiple scan lines, then processed by spatial Fourier analysis to estimate the predominant wave speed and analyzed by algebraic wavefield inversion to reconstruct wave speed maps. Reconstructions of shear wave speed from simulated wavefields illustrate the accuracy and spatial resolution available with both methods, as functions of signal-to-noise ratio and sizes of windows used for Fourier analysis or wavefield smoothing. The methods are applied to shear wavefields with frequencies up to six times the Nyquist rate, thus extending the frequency range measurable by a given imaging system. Wave speed measurements in tissue-mimicking phantoms are compared with supersonic shear imaging and mechanical tensile testing, demonstrating feasibility of the wavefield measurement and wave speed reconstruction methods employed.

A survey of current clinical practice in permanent and temporary prostate brachytherapy: 2010 update.

PURPOSE: To help establish patterns of care and standards of care of interstitial permanent low-dose-rate (LDR) and temporary high-dose-rate brachytherapy for prostate cancer and to compare the results with a similar 1998 American Brachytherapy Society (ABS) survey. METHODS AND MATERIALS: A comprehensive questionnaire intended to survey specific details of current clinical brachytherapy practice was provided to the participants of the seventh ABS Prostate Brachytherapy School. Responses were tabulated and descriptive statistics are reported. RESULTS: Sixty-five brachytherapy practitioners responded to the survey. Eighty-nine percent (89%) of respondents performed LDR and 49% perform high-dose-rate brachytherapy. The median number of years of experience for LDR brachytherapists increased from 5 to 10 years over the course of the 12 years since the preceding survey. Compared with the first ABS, a smaller proportion of respondents received formal brachytherapy residency training (43% vs. 56%) or formal "hands-on" brachytherapy training (15% vs. 63%). There has been a marked decline in the utilization of the Mick applicator (Mick Radio-Nuclear Instruments, Inc., Mount Vernon, NY, USA) (60% vs. 28%) and an increase in the use of stranded seeds (40% vs. 11%). Compliance with postimplant dosimetry was higher in the 2010 survey. CONCLUSION: This survey does suggest an evolution in the practice of LDR brachytherapy since 1998 and aids in identifying aspects that require further progress or investigation. ABS guidelines and other practice recommendations appear to impact the practice of brachytherapy.

American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy.

PURPOSE: To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB). METHODS AND MATERIALS: The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS. RESULTS: Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography-based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography-magnetic resonance image fusion is viewed as useful, but not mandatory. CONCLUSIONS: Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians.

Fifteen-year biochemical relapse-free survival, cause-specific survival, and overall survival following I(125) prostate brachytherapy in clinically localized prostate cancer: Seattle experience.

PURPOSE: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I(125) brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. METHODS AND MATERIALS: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I(125) monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. RESULTS: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. CONCLUSION: I(125) monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

Permanent prostate brachytherapy preplanned technique: The modern Seattle method step-by-step and dosimetric outcomes.

PURPOSE: To describe, step-by-step, the current Seattle preplan technique, and report the dosimetric outcomes on 1,131 consecutively such treated prostate brachytherapy patients. METHODS AND MATERIALS: One thousand one hundred thirty one patients with prostate cancer were treated with iodine-125 ((125)I), palladium-103 ((103)Pd), or cesium-131 ((131)Cs) using a preplanned template-guided transrectal ultrasound-guided approach between January 2005 and August 2007. Day one computed tomography (CT) scans were taken for postimplantation dose-volume histogram evaluations. Postoperative prostate contours were drawn by one author (DN) on CT images taken on postoperative day one. RESULTS: The volume of prostate receiving 100% of prescription dose (V(100)) and percent dose to 90% of the prostate (%D(90)) were 95% and 106% for 558 monotherapy (125)I implants, 91% and 102% for 327 (103)Pd implants, and 97% and 111.5% for 13 (131)Cs implants, respectively. The median V(100) and percent D(90) were 91% and 101% for five boost (125)I implants, 92% and 104% for 228 boost (103)Pd implants. The median rectal volume receiving 100% of prescription dose (RV(100)) for (125)I, (103)Pd, and (131)Cs monotherapy implants were 0.3, 0.13, and 0.38cc, and for (125)I and (103)Pd boost implants were 0.16 and 0.13cc, respectively. No patient received an RV(100) of >0.92cc. CONCLUSIONS: Modern preplanned template and ultrasound-guided prostate brachytherapy can consistently result in excellent prostate dosimetry and rectal sparing.

Analysis of the Pro-Qura Database: rectal dose, implant quality, and brachytherapist's experience.

PURPOSE: This study analyzed rectal dosimetry outcomes of Pro-Qura proctored implants to assess the achievability of proposed rectal dose constraints in the setting of standardized pre- and postimplant dosimetry in community-based brachytherapy programs. METHODS AND MATERIALS: From August 2005 to July 2007, 713 postimplant CT scans were evaluated from 26 brachytherapists actively participating in Pro-Qura. Postimplant dosimetry was performed in a standardized fashion. The entirety of the rectal wall was contoured and evaluated for dose. Rectal dose was defined in terms of the volume of the rectum receiving 100% of the prescription dose (R(100)). Criteria for implant adequacy for both (103)Pd and (125)I included a prostate the percentage of the prostate volume covered by the prescription dose (V(100))>80%, a prostate the maximum dose covering 90% of the prostate volume (D(90)) of 90-140%, and an R(100)<1.0cm(3) for early (Day 0-7) dosimetry and <1.3cm(3) for late (Day 20-45) dosimetry. RESULTS: Mean prostatic volume was 35.1cm(3). The mean time from implant to CT scan was 29.9 days (range, 0-45 days). The respective mean overall prostate V(100) and D(90) were 89% and 101%, respectively, and remained consistent for sequence groups 1 through 6. Overall, the mean R(100) was 0.97+/-1.04cm(3). The R(100) was 1.15cm(3) for sequence Group 1 and with each subsequent sequence group decreased with a nadir of 0.83cm(3) in sequence Group 6 (p=0.22). Rectal dosimetry was deemed inadequate in 39% of Group 1 implants but only 22% in Group 6 (p=0.016). The reduced rectal doses did not impact prostate gland coverage. CONCLUSIONS: Using standardized dosimetry, R(100) improved with increasing brachytherapist's experience, reaching a plateau after approximately 20 patients.

Interstitial implant alone or in combination with external beam radiation therapy for intermediate-risk prostate cancer: a survey of practice patterns in the United States.

PURPOSE: This study is aimed at understanding and defining the current patterns of care with respect to prostate brachytherapy for patients with intermediate-risk localized disease in the combined academic and community setting. METHODS AND MATERIALS: A nomogram-based survey was developed at the Seattle Prostate Institute defining the accepted criteria for intermediate-risk prostate cancer. Patients were defined as having intermediate-risk prostate cancer if they met one of the following criteria: prostate-specific antigen (PSA) >10 ng/dL, Gleason score (GS) > or = 7, or cT2b or cT2c disease. Additional potential predictive factors including perineural invasion (PNI), GS 3+4 vs. 4+3, and high-volume disease were included. RESULTS: In the absence of PNI, all of those surveyed would perform monotherapy for intermediate-risk patients, GS 7 (3+4) or PSA 10-20, with cT1c and <30% cores +. Up to 80% would perform monotherapy for patients with cT1c, GS 7 (4+3), and <30% cores +. Eighty to 90% of physicians would perform an implant alone with cT2a and either a PSA of 10-20 or GS of 7 (3+4) and <30% cores +. Fifty to 60% of those surveyed stated that they would treat a patient with cT2b disease, GS 7 (3+4), or PSA 11-20, with less than two-thirds of the biopsy cores positive in the absence of PNI. CONCLUSIONS: This Patterns of Care (POC) study reveals that certain subsets of intermediate-risk localized prostate cancer patients are considered appropriate candidates for an interstitial implant alone.

Initial analysis of Pro-Qura: a multi-institutional database of prostate brachytherapy dosimetry.

PURPOSE: The study aimed to analyze the Pro-Qura database in terms of patient implant sequence number for each institution to determine evidence for a dosimetric learning curve. METHODS AND MATERIALS: In the Pro-Qura database, 2833 of a total of 4614 postplans from 57 brachytherapists were analyzed for evidence of a dosimetric learning curve. The median time between implant and postimplant CT scan was 30 days. I-125 was used in 2123 patients (1687 monotherapy and 536 boost) and Pd-103 in 710 patients (367 monotherapy and 343 boost). Preimplant prostate volume was 35.3 and 32.9 cm3 in the I-125 and Pd-103 cohorts, respectively. The mean I-125 seed activity was 0.32 and 0.26 mCi for monotherapy and boost, whereas for Pd-103 the mean seed activity was 1.59 and 1.27 mCi, respectively. Postimplant dosimetry was performed in a standardized fashion by overlaying the preimplant ultrasound and the postimplant CT scan. Criteria for implant adequacy included a D90 >90% and a V100 >80% for both isotopes. An adequate V150 was defined as <60% for I-125 and <75% for Pd-103. RESULTS: The mean V100 and D90 were 88.9% and 101.9% of prescription dose, respectively. When analyzed in terms of patient sequence number for each institution, the mean V100 for the first 10 patients was 87.4% and increased to 88.6% for patients 11-20 (p = 0.036). Similarly, the mean D90 for the first 10 patients was 98.9%, whereas for the second cohort of 10 patients the mean D90 increased to 102.2% (p = 0.001). In terms of mean V100 and D90, there was minimal further change for subsequent 10 patient institutional groupings of patient sequence numbers. For the first 10 cases, 27.2% were deemed "too cool" (V100 <80% and/or D90 <90%). Approximately 16% of all implants were deemed "too hot" (D90 >140% or V150 >60% for I-125 or >75% for Pd-103). CONCLUSIONS: Although a learning curve exists for prostate brachytherapy, high-quality brachytherapy is achievable in approximately 75-80% of patients treated at community centers.

15-Year biochemical relapse free survival in clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience.

PURPOSE: Long-term biochemical relapse-free survival (BRFS) rates in patients with clinical Stages T1-T3 prostate cancer continue to be scrutinized after treatment with external beam radiation therapy and brachytherapy. METHODS AND MATERIALS: We report 15-year BRFS rates on 223 patients with clinically localized prostate cancer that were consecutively treated with I(125) or Pd (103) brachytherapy after 45-Gy neoadjuvant EBRT. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified American Society for Therapeutic Radiology and Oncology consensus definition (two consecutive serum prostate-specific antigen rises) as the outcome. Gleason scoring was performed by the pathologists at a community hospital. Time to biochemical failure was calculated and compared by using Kaplan-Meier plots. RESULTS: Fifteen-year BRFS for the entire treatment group was 74%. BRFS using the Memorial Sloan-Kettering risk cohort analysis (95% confidence interval): low risk, 88%, intermediate risk 80%, and high risk 53%. Grouping by the risk classification described by D'Amico, the BRFS was: low risk 85.8%, intermediate risk 80.3%, and high risk 67.8% (p = 0.002). CONCLUSIONS: I(125) or Pd(103) brachytherapy combined with supplemental EBRT results in excellent 15-year biochemical control. Different risk group classification schemes lead to different BRFS results in the high-risk group cohorts.

Second malignancies after prostate brachytherapy: incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up.

PURPOSE: To report the incidence of second bladder and colorectal cancers after prostate brachytherapy. METHODS AND MATERIALS: This review included 125 patients treated with I-125 brachytherapy alone, and 223 patients who received supplemental external beam radiation therapy. Median follow-up was 10.5 years. Patients were followed for the development of lower genitourinary and colorectal cancers. Second malignancies arising five years after radiation therapy were defined as being potentially associated with treatment; observed rates were then compared with age-matched expected rates according to Surveillance, Epidemiology, and End Results data. RESULTS: Five years out of treatment, there were 15 patients with a second solid tumor, including bladder cancer (n = 11), colorectal cancer (n = 3), and prostatic urethra cancer (n = 1). The incidence of second malignancy was no different in patients treated with brachytherapy alone (1.6%) vs. those receiving external beam radiotherapy (5.8%, p = 0.0623). There were more observed bladder cancers compared with those expected (relative risk, 2.34, 95% confidence interval 0.96-3.72; absolute excess risk 35 cancers per 10,000 patients). Relative risk did not significantly change over increasing follow-up intervals up to 20 years after treatment. CONCLUSIONS: There may be an increased but small risk of developing a second malignancy after radiation therapy for prostate cancer. This outcome could be related to radiation carcinogenesis, but more vigilant screening and thorough workup as a result of radiation side effects and predisposing conditions (e.g., genetic and environmental factors) in many of the patients found to have second malignancies likely contributed to the higher number of observed malignancies than expected.

Technical improvement in permanent seed implantation: a two-stage brachytherapy system. Description and comparison with current technique.

PURPOSE: Permanent seed implantation by available techniques has modest limitations. A new, two-stage needle design and technique is described and evaluated in comparison to a conventional permanent seed technique. METHODS AND MATERIALS: The technique involves placing a stylet and sleeve initially into the all target coordinates prior to seed placement similar to temporary seed technique. The second stage involves consecutively removing the stylet from each sleeve and inserting a clear, plastic needle containing preloaded seeds into the sleeve and implanting the seeds. Fifty-six (125)I patients were treated with the two-stage technique. Comparisons were made with a cohort of 71 patients implanted using a conventional technique at the Seattle Prostate Institute. Prostate movement, surgical time, catheterization rate, and DVH postop dosimetry were analyzed. RESULTS: After an initial learning curve, the two-stage technique had surgical times similar to conventional techniques. Cephalad movement of 3-10 mm was noted in 4 (8%) patients vs. 71 (100%) patients with our conventional technique. Of the 6 (10%) patients who required Foley catheterization, 3 (5%) did so for 1 day and 3 (5%) did so for less than 3 weeks. Day 1 CT scan based dosimetry was calculated on all patients. The V100 ranged from 80-100% with a median of 92.5%. For primary cases, the V100 (<85%) was 14% for the conventional vs. 7% for the two-stage technique. No two-stage patient had a V100 <80%. The V100 values for the two-stage and conventional techniques demonstrated a possible advantage with the two-stage technique (mean V100 92.6% vs. 90.7%, [p=0.051]). The D90 for the two-stage technique ranged from 123-190 Gy with a median of 151.5 Gy for implant only and a median of 127 Gy for boost cases. The D90 values for the two-stage patients were slightly but not statistically better than the conventional technique (p=0.232). Thirty-one percent of conventional technique patients had a D90 <140 Gy vs. 22% for two-stage technique. CONCLUSION: This new two-stage brachytherapy technique may offer some advantages over conventional techniques including: simple and improved needle loading verification, less complicated and better visualization of needle placement, improved stabilization of the gland, and more consistent postoperative dosimetry.

Ten-year biochemical relapse-free survival after external beam radiation and brachytherapy for localized prostate cancer: the Seattle experience.

PURPOSE: The role of external beam radiation therapy in addition to brachytherapy continues to be scrutinized for long term control of PSA levels after prostate cancer diagnosis. METHODS AND MATERIALS: We report 10-year biochemical relapse-free survival (BRFS) on 232 patients presenting with localized prostate cancer and consecutively treated with iodine(125) (I(125)) or palladium(103) (Pd(103)) brachytherapy and neoadjuvant external beam radiation therapy. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified ASTRO consensus definition (two consecutive rises in serum PSA) as the outcome. Gleason scoring was performed by pathologists at a small community hospital. Derived risk categories are the following: low = PSA 10 ng/mL or Gleason Score >or=7 or stage >or=T2c (1 intermediate risk factor); and high = 2 or more intermediate risk factors. Time to PSA failure (local, distant, or biochemical) was calculated and compared using Kaplan-Meier plots. RESULTS: Ten-year BRFS for the entire treatment group was 70%. Biochemical control rates by risk cohort analysis (95% confidence interval): low risk, 85% (83.3-90.7%); intermediate risk, 77% (73.0-84.5%); and high risk, 45% (45.4-57.2%). Using a risk grouping proposed by the Mt. Sinai group, the BRFS was: low risk, 84%; intermediate risk, 93%; and high risk, 57%. Grouping by the risk classification used by D'Amico, the BRFS was: low risk, 86%; intermediate risk, 90%; and high risk, 48%. CONCLUSIONS: I(125) or Pd(103) brachytherapy, as a boost combined with EBRT, continues to result in high rates of biochemical control at 10 years. Different risk group classification schemes lead to different BRFS results.

Adjuvant chemohormonal therapy of high risk prostate carcinoma. Ten year results.

BACKGROUND: Patients with T3 and/or N1 prostate carcinoma have poor cure rates. The authors sought to improve the relapse free, cancer specific survival of these patients by adding chemohormonal therapy to radiation. METHODS: Twenty-five men with clinical Stage III positive seminal vesicles or positive nodes received six courses of vinblastine, doxorubicin, and mitomycin with simultaneous radiation and permanent androgen deprivation. Prostate specific antigen (PSA) testing was the sole criterion for relapse. Median followup was 10.5 years. RESULTS: Treatment was well tolerated. Patients received 91-95% of each drug and all planned radiation. At 10 years the cumulative relapse free rate determined by continuously undetectable PSA levels was 73%, and the cumulative cancer specific survival was 81%. Of node-positive patients, 82% were relapse-free at 10 years. CONCLUSIONS: The addition of chemotherapy to hormonal and radiation therapy is feasible and is accepted by most men when they are openly informed of their prognosis with conventional therapy. Results in the current small series appear excellent and may be superior to radiation plus hormones alone. Larger randomized studies are warranted.

Brachytherapy for carcinoma of the prostate: techniques, patient selection, and clinical outcomes.

Brachytherapy for prostate carcinoma has developed as either low dose rate permanent implants or high dose rate afterloading. Both approaches offer unsurpassed dose escalation and, particularly with permanent implants, the convenience of a single outpatient treatment. These therapies have now entered the mainstream of treatment options and are in the refinement phase of development. Techniques of implantation, treatment planning approaches, innovative fractionation schemes, and appropriate patient selection are the subject of current investigation. Treatment results are available beyond 10 years and appear equivalent or superior to other modalities. Although short term morbidity can be significant with brachytherapy, most current series report low long-term urinary and rectal complications. Meaningful quality of life studies and randomized cooperative group trials are now underway and should help define the role of brachytherapy in the near future.